Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas

Colorectal adenocarcinoma (COREAD) is the second most deadly cancer and third most frequently encountered malignancy worldwide. Despite efforts in molecular subtyping and subsequent personalized COREAD treatments, multidisciplinary evidence suggests separating COREAD into colon cancer (COAD) and rec...

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Main Authors: Jennyfer M. García-Cárdenas, Isaac Armendáriz-Castillo, Nathali García-Cárdenas, David Pesantez-Coronel, Andrés López-Cortés, Alberto Indacochea, Santiago Guerrero
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2023.1088057/full
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author Jennyfer M. García-Cárdenas
Jennyfer M. García-Cárdenas
Isaac Armendáriz-Castillo
Isaac Armendáriz-Castillo
Isaac Armendáriz-Castillo
Nathali García-Cárdenas
David Pesantez-Coronel
Andrés López-Cortés
Andrés López-Cortés
Alberto Indacochea
Santiago Guerrero
Santiago Guerrero
author_facet Jennyfer M. García-Cárdenas
Jennyfer M. García-Cárdenas
Isaac Armendáriz-Castillo
Isaac Armendáriz-Castillo
Isaac Armendáriz-Castillo
Nathali García-Cárdenas
David Pesantez-Coronel
Andrés López-Cortés
Andrés López-Cortés
Alberto Indacochea
Santiago Guerrero
Santiago Guerrero
author_sort Jennyfer M. García-Cárdenas
collection DOAJ
description Colorectal adenocarcinoma (COREAD) is the second most deadly cancer and third most frequently encountered malignancy worldwide. Despite efforts in molecular subtyping and subsequent personalized COREAD treatments, multidisciplinary evidence suggests separating COREAD into colon cancer (COAD) and rectal cancer (READ). This new perspective could improve diagnosis and treatment of both carcinomas. RNA-binding proteins (RBPs), as critical regulators of every hallmark of cancer, could fulfill the need to identify sensitive biomarkers for COAD and READ separately. To detect new RBPs involved in COAD and READ progression, here we used a multidata integration strategy to prioritize tumorigenic RBPs. We analyzed and integrated 1) RBPs genomic and transcriptomic alterations from 488 COAD and 155 READ patients, 2) ∼ 10,000 raw associations between RBPs and cancer genes, 3) ∼ 15,000 immunostainings, and 4) loss-of-function screens performed in 102 COREAD cell lines. Thus, we unraveled new putative roles of NOP56, RBM12, NAT10, FKBP1A, EMG1, and CSE1L in COAD and READ progression. Interestingly, FKBP1A and EMG1 have never been related with any of these carcinomas but presented tumorigenic features in other cancer types. Subsequent survival analyses highlighted the clinical relevance of FKBP1A, NOP56, and NAT10 mRNA expression to predict poor prognosis in COREAD and COAD patients. Further research should be performed to validate their clinical potential and to elucidate their molecular mechanisms underlying these malignancies.
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spelling doaj.art-3015456131ee4859baff92877cfba7c72023-06-13T04:19:40ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-06-011110.3389/fcell.2023.10880571088057Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomasJennyfer M. García-Cárdenas0Jennyfer M. García-Cárdenas1Isaac Armendáriz-Castillo2Isaac Armendáriz-Castillo3Isaac Armendáriz-Castillo4Nathali García-Cárdenas5David Pesantez-Coronel6Andrés López-Cortés7Andrés López-Cortés8Alberto Indacochea9Santiago Guerrero10Santiago Guerrero11Laboratorio de Ciencia de Datos Biomédicos, Escuela de Medicina, Facultad de Ciencias Médicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito, EcuadorLatin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, SpainLaboratorio de Ciencia de Datos Biomédicos, Escuela de Medicina, Facultad de Ciencias Médicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito, EcuadorLatin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, SpainFacultad de Ingenierías y Ciencias Aplicadas, Universidad Internacional SEK, Quito, EcuadorInstituto Nacional de Investigación en Salud Pública, Quito, EcuadorMedical Oncology Department Hospital Clinic and Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, SpainLatin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, SpainCancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, EcuadorMedical Oncology Department Hospital Clinic and Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, SpainLaboratorio de Ciencia de Datos Biomédicos, Escuela de Medicina, Facultad de Ciencias Médicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito, EcuadorLatin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, SpainColorectal adenocarcinoma (COREAD) is the second most deadly cancer and third most frequently encountered malignancy worldwide. Despite efforts in molecular subtyping and subsequent personalized COREAD treatments, multidisciplinary evidence suggests separating COREAD into colon cancer (COAD) and rectal cancer (READ). This new perspective could improve diagnosis and treatment of both carcinomas. RNA-binding proteins (RBPs), as critical regulators of every hallmark of cancer, could fulfill the need to identify sensitive biomarkers for COAD and READ separately. To detect new RBPs involved in COAD and READ progression, here we used a multidata integration strategy to prioritize tumorigenic RBPs. We analyzed and integrated 1) RBPs genomic and transcriptomic alterations from 488 COAD and 155 READ patients, 2) ∼ 10,000 raw associations between RBPs and cancer genes, 3) ∼ 15,000 immunostainings, and 4) loss-of-function screens performed in 102 COREAD cell lines. Thus, we unraveled new putative roles of NOP56, RBM12, NAT10, FKBP1A, EMG1, and CSE1L in COAD and READ progression. Interestingly, FKBP1A and EMG1 have never been related with any of these carcinomas but presented tumorigenic features in other cancer types. Subsequent survival analyses highlighted the clinical relevance of FKBP1A, NOP56, and NAT10 mRNA expression to predict poor prognosis in COREAD and COAD patients. Further research should be performed to validate their clinical potential and to elucidate their molecular mechanisms underlying these malignancies.https://www.frontiersin.org/articles/10.3389/fcell.2023.1088057/fullRNA-binding proteins (RBPs)colorectal adenocarcinoma (COREAD)rectumcolonbiomarkerscancer
spellingShingle Jennyfer M. García-Cárdenas
Jennyfer M. García-Cárdenas
Isaac Armendáriz-Castillo
Isaac Armendáriz-Castillo
Isaac Armendáriz-Castillo
Nathali García-Cárdenas
David Pesantez-Coronel
Andrés López-Cortés
Andrés López-Cortés
Alberto Indacochea
Santiago Guerrero
Santiago Guerrero
Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas
Frontiers in Cell and Developmental Biology
RNA-binding proteins (RBPs)
colorectal adenocarcinoma (COREAD)
rectum
colon
biomarkers
cancer
title Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas
title_full Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas
title_fullStr Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas
title_full_unstemmed Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas
title_short Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas
title_sort data mining identifies novel rna binding proteins involved in colon and rectal carcinomas
topic RNA-binding proteins (RBPs)
colorectal adenocarcinoma (COREAD)
rectum
colon
biomarkers
cancer
url https://www.frontiersin.org/articles/10.3389/fcell.2023.1088057/full
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